Efflux Impacts Intracellular Accumulation Only in Actively Growing Bacterial Cells

Author:

Whittle Emily E.1,McNeil Helen E.1,Trampari Eleftheria2,Webber Mark2,Overton Tim W.3,Blair Jessica M. A.1ORCID

Affiliation:

1. College of Medical and Dental Sciences, Institute of Microbiology and Infection, University of Birmingham, Birmingham, United Kingdom

2. Quadram Institute Bioscience, Norwich, United Kingdom

3. School of Chemical Engineering, University of Birmingham, Birmingham, United Kingdom

Abstract

This study shows that efflux is important for maintaining low intracellular accumulation only in actively growing cells and that envelope permeability is the predominant factor in stationary-phase cells. This conclusion means that (i) antibiotics with intracellular targets may be less effective in complex infections with nongrowing or slow-growing bacteria, where intracellular accumulation may be low; (ii) efflux inhibitors may be successful in potentiating the activity of existing antibiotics, but potentially only for bacterial infections where cells are actively growing; and (iii) the remodeling of the cell envelope prior to stationary phase could provide novel drug targets.

Funder

UKRI | Biotechnology and Biological Sciences Research Council

Wellcome

Publisher

American Society for Microbiology

Subject

Virology,Microbiology

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